Cefmetazole sodium has the chemical name (6R,7S)-3-{[(1-methyl-1H-tetrazol-5-yl)thio]methyl}-7-[2-(thiocyanomethyl)acetamido]-7-methoxy-S-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-formic acid sodium salt and a molecular formula of C15H16N7NaO5S3 with a molecular weight of 493.52. The content of Cefmetazole sodium is not less than 86.0%, calculated on the anhydrous. The structure of Cefmetazole sodium is as follows:
Cefmetazole sodium is a second generation cephalosporin, and is more stable towards broad-spectrum β-lactamase generated by negative bacilli. It shows relatively good activity against negative bacilli such as Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Shigella, Salmonella, etc., high sensitivity to Staphylococcus aureus, group A hemolytic streptococcus and catarrhal Brenham bacteria, good antibacterial activity against Bacteroides fragilis, and low sensitivity or resistance to Enterobacter, Pseudomonas, methicillin-resistant Staphylococcus aureus, pneumococcus, and meningococcus. It is clinically useful for the treatment of various infections induced by sensitive bacteria, such as respiratory infections, biliary tract infections, urinary tract infections, obstetrics and gynecology bacterial infections, skin and soft tissue infections, and prevention of post-operative infections.
A number of domestic and foreign references of patents and journals have disclosed processes for preparing and refining Cefmetazole sodium.
Chinese Patent CN101550151A discloses a process for preparing Cefmetazole sodium, wherein 7β-amino-7α-methoxy-3-(1-methyl-1H-tetrazol-5-thiomethyl)-3-cephem-4-carboxylic acid benzyl ester is mixed and reacted with sodium cyanomethylthioacetate in the presence of p-toluenesulfonyl chloride, generating Cefmetazole, which is treated with added sodium hydroxide to form Cefmetazole sodium. However, the yield and the purity of Cefmetazole sodium prepared by this method are low.
Chinese Patent CN101787039A reports a process for preparing and refining Cefmetazole sodium. Although the purity of Cefmetazole sodium is improved, the inherent impurities in the drug substance is difficult to separate by simple reconciling with acids and bases, and additional negative ion impurities may be introduced in the pH adjusting process, thereby increasing the difficulties in separation.
Currently, Cefmetazole sodium is manufactured mainly dependent on dispensing from imported raw material drugs by domestic pharmaceutical manufacturers. Although Cefmetazole sodium is produced in China, however, both the yield and the product purity are still low. Therefore, how to improve the purity of Cefmetazole sodium is a pending problem anxiously to be solved, which possesses significant social and economic benefits.